Sodium channel molecular conformations and antiarrhythmic drug affinity.
Sodium channel molecular conformations and antiarrhythmic drug affinity.
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DOI：
10.1016/j.tcm.2010.03.002
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发表时间：
2010-01
影响因子：
9.3
通讯作者：
Hanck, Dorothy A.
中科院分区：
文献类型：
--
作者：
Sheets, Michael F.;Fozzard, Harry A.;Lipkind, Gregory M.;Hanck, Dorothy A.
由于存在使用依赖性阻滞，I类心脏抗心律失常药物，例如利多卡因、美西律、氟卡尼、奎尼丁和普鲁卡因胺，在心律失常的治疗中继续发挥重要作用。利多卡因，以及相关药物如甲哌卡因，布比卡因和可卡因，也属于被称为局部麻醉剂的药物类别。在这篇综述中，我们将考虑利多卡因作为原型抗癫痫药物，因为它继续被广泛用作抗癫痫药物（1950年首次用作抗癫痫药物）以及局部麻醉剂。这两种临床用途都依赖于钠电流（INa）的阻滞，但正是存在使用依赖性INa阻滞，即在心率加快时阻滞量增加，才使局部麻醉剂成为有用的抗心律失常药物。虽然许多早期的研究调查的抗血小板药物对钠电流的作用，定点突变的钠通道的可用性，使重大进展，了解其作用机制的基础上的分子构象的钠通道。
Class I cardiac antiarrhythmic drugs, e.g. lidocaine, mexiletine, flecainide, quinidine, and procainamide, continue to play an important role in the therapy of cardiac arrhythmias because of the presence of use-dependent block. Lidocaine, as well as related drugs like mepivacaine, bupivacaine, and cocaine, also belong to the class of medications referred to as local anesthetics. In this review we will consider lidocaine as the prototypical antiarrhythmic drug because it continues to be widely used both as an antiarrhythmic drug (first used as an antiarrhythmic drug in 1950) as well as a local anesthetic agent. Both of these clinical uses depend upon block of sodium current (INa), but it is the presence of use-dependent INa block, i.e. an increasing amount of block at faster heart rates, that allows a local anesthetic agent to be a useful antiarrhythmic drug. Although many early studies investigated the action of antiarrhythmic drugs on Na currents, the availability of site-directed mutant Na channels has allowed for major advances in understanding their mechanisms of action based upon molecular conformations of the Na channel.
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